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Biomedical subjects

R J Deckelbaum

Publications and source records attributed to R J Deckelbaum.

At least 127 records · Page 7Linked to original sources
PubMed1987

Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B. Chylomicron retention disease.

Eight infants presented with a malabsorption syndrome, normal fasting triglycerides, hypocholesterolemia (64.3 +/- 10.0 mg/dl), and deficiency of vitamins A and E. Plasma low-density lipoprotein, apolipoprotein B, and apolipoprotein A-I were decreased. After a fatty meal, plasma triglycerides did not increase and chylomicrons could not be identified. Lipoprotein composition was characterized by normal apoproteins, high phospholipids, and low cholesterol. Increased triglycerides were present in low-density lipoproteins. Immunoperoxidase localization of apolipoprotein B on fasting biopsy specimens showed increased staining of the lipid-laden intestinal epithelial cells compared to normals. On electron microscopy after a fat load, the enterocytes contained large numbers of fat particles vesiculating the endoplasmic reticulum. These particles, morphologically similar to chylomicrons, were also present as aggregates of well-individualized lipid droplets within dilated vesicles in the Golgi zone, but were not seen in the intercellular spaces and lacteals. This recessively transmitted condition differs from abetalipoproteinemia and from the homozygous form of hypobetalipoproteinemia and may be caused by a defect in the final assembly of chylomicrons or in the mechanism of their exocytosis.

Apolipoproteins B↗
PubMed1987

Interactions between exogenous fat and plasma/lipoproteins.

Fat emulsions are essentially composed of triglycerides and phospholipids. Their elimination from the plasma--which is generally rapid--is influenced by the amount and the composition of both these components. During their short stay in the vascular compartment, exogenous particles undergo major compositional changes. They acquire various apolipoproteins--namely C-II, C-III, E and A-IV--by transfer from HDL. They also acquire esterified cholesterol from HDL and LDL and transfer exogenous triglycerides and phospholipids to these endogenous lipoproteins. These exchanges are affected by the type of triglyceride fatty acids and the amount of phospholipids present in fat emulsions, as well as by the infusion rate. Some 10% of emulsions--with a high phospholipid: triglyceride ratio--contain a huge phospholipid excess which can be isolated as a separate fraction from the triglyceride-rich particles. These phospholipids markedly interfere with the metabolism of cholesterol and the plasma lipoprotein profile.

Cholesterol↗
PubMed1987

Intestinal apoB synthesis, lipids, and lipoproteins in chylomicron retention disease.

Chylomicron retention disease is characterized by fat malabsorption, hypocholesterolemia, normal fasting triglycerides, and marked intestinal steatosis despite the presence of both plasma and intestinal apoprotein B. The defect remains unknown but presumably involves the synthesis or secretion of chylomicrons. The present investigation examines this hypothesis by studying the biosynthesis of chylomicrons in cultured jejunal explants and by defining the quantitative and qualitative abnormalities of plasma lipids and of circulating lipoproteins. Following 2-3 years of a low fat diet supplemented with medium chain triglycerides, six patients with chylomicron retention disease had significantly higher triglyceride (TG) levels coupled with a decrease in both free (FC) and esterified cholesterol (EC) as well as in essential fatty acids and phospholipids (PL) when compared to healthy controls. The low total plasma cholesterol was largely accounted for by low levels of both low density (LDL) and high density lipoprotein (HDL) cholesterol. VLDL and LDL were characterized by a diminished percentage of CE with an increase of TG while HDL contained relatively more FC as well as PL and less CE. The diameter of VLDL was larger whereas those of LDL and HDL were smaller than in normal controls. Jejunal explants, when incubated with [14C]palmitate, were capable of normal biosynthesis of TG, diglycerides, PL, and CE. These lipids, however, except for PL, were retained in the tissue and could not be secreted into the culture medium. Incubation of intestinal biopsies with [3H]leucine and [14C]mannose resulted in normal protein synthesis and reduced glycosylation. The presence of intestinal apoB-48 was confirmed by immunoblot using 2D8 antibodies. These data suggest that the intestinal defect in this disease results from a disorder of the final assembly of chylomicrons or in the mechanism of their exocytosis.

Apolipoproteins B↗
PubMed1986

Conversion of human plasma high density lipoprotein-2 to high density lipoprotein-3. Roles of neutral lipid exchange and triglyceride lipases.

Cholesterol esters accumulating in human plasma high density lipoproteins (HDL) are important in conversion of HDL3 to larger HDL2. We studied whether mechanisms of removal of cholesterol esters from HDL might be important in a reverse direction, i.e. conversion of HDL2 to HDL3. Native HDL2 or HDL3 is incubated with very low density lipoproteins (VLDL) and lipoprotein-poor plasma (d greater than 1.21 g/ml) at 37 degrees C. After incubation, "modified" (M) VLDL, and HDL2 or HDL3 are reisolated by ultracentrifugation. In modified M-HDL2 or M-HDL3, triglyceride becomes the major core lipid as the triglyceride/cholesterol ester weight ratio increases 8-10-fold relative to native HDL. With only small changes in protein/phospholipid ratios in M-HDLs, the large decrease in cholesterol ester/protein ratios suggest net cholesterol ester loss from HDL. Quantitative recovery analyses prove that the cholesterol esters lost from HDL are transferred to M-VLDL, which is now richer in cholesterol ester and poorer in triglyceride. These substantial exchanges of HDL lipids are not associated by significant transfer of HDL apoproteins but are dependent on neutral lipid transfer factors present in human lipoprotein-poor plasma (d greater than 1.21 g/ml). Similar results are obtained when purified core lipid transfer protein replaces d greater than 1.21 g/ml plasma in these incubations. After depletion of cholesterol ester from HDL, most but not all, exchanged triglyceride can be removed by lipolysis with either hepatic or lipoprotein lipase, resulting in a post-lipolysis HDL2 with an increased triglyceride content relative to normal HDL. With successive incubations with VLDL, and core lipid transfer factors, HDL2 loses more than two-thirds of its cholesterol esters. After lipolysis of acquired triglyceride, HDL2 is remodeled, in both composition and flotation parameters, toward HDL3.

Apoproteins↗
PubMed1986

Giardia lamblia: identification of different strains from man.

Four axenically cultured human Giardia lamblia isolates from Jerusalem (KC-1, 2, 3 and 4) and one from Bethesda (WB) were compared. Three distinct groups were defined by agglutination response to rabbit anti-G. lamblia sera viz. WB; KC-3; and KC-1, 2 and 4. The same major groups were identified by isoenzyme analysis using thin-layer starch-gel electrophoresis, each group differing from the others in three or more of five enzymes studied. In addition, a single enzyme difference distinguished KC-2 from KC-1 and 4. These findings reveal significant heterogeneity in G. lamblia isolates both from widely separated areas and within a single region. Immunoassays for diagnosis of giardiasis should take into account the differences between strains. Heterogeneity among G. lamblia strains may explain the variable clinical manifestations, host response and treatment efficacy characteristic of human giardiasis.

Agglutination Tests↗
PubMed1986

Two-hour lactose breath hydrogen test.

Current requirements for the lactose breath hydrogen test (LBHT) include serial expired air samplings and multiple hydrogen (H2) determinations. One hundred thirty-two consecutive LBHTs were evaluated to determine whether multiple samplings are indeed necessary for detection of lactose malabsorption. Expired air samples were collected at 0, 30, 60, 90, 120, 150, and 180 min following ingestion of lactose. Fifty-five LBHTs were positive for lactose malabsorption. All tests showed abnormally elevated breath H2 concentrations at 120 min. The mean value of the change in parts per million (delta ppm) of H2 at 120 min (51.1 +/- 4.7 SEM) was higher than at any other time point. If only the 120-min samples were examined without subtracting the initial concentrations, four of the 77 negative tests (5.2%) would have been falsely positive. Thus, the values of H2 at 0 and 120 min were sufficient to define lactose malabsorption in all cases. We conclude that just as a single blood sample now suffices for determining xylose malabsorption, so expired air sampling at only 0 and 120 min during the LBHT is a reliable method for detecting lactose malabsorption and diminishes the need for acquiring and analyzing multiple samples.

Adolescent↗
PubMed1986

Fat emulsions are more than energy suppliers.

The type of triglycerides in exogenous fat emulsions as well as the phospholipid: triglyceride ratio influences the plasma clearance. The plasma clearance cannot be used for indicating the utilization of fat emulsions as energy substrate. Introducing exogenous fat in replacement of part of the calories provided by glucose reduces a series of complications associated with large glucose intake. There are exchanges of triglycerides, esterified cholesterol, phospholipids and apoproteins between exogenous lipids and endogenous lipoproteins, depending on the composition of exogenous lipid emulsions. These interactions can significantly modify the composition of both, exogenous particles and endogenous lipoproteins. In future it will become essential to determine the removal site of 'exogenous remnants'. Future progress will allow a better understanding of the influence of these modifications on the metabolism of endogenous lipoproteins and the utilization of exogenous fat emulsions.

Apoproteins↗
PubMed1985

Core modification of human low-density lipoprotein by artificial triacylglycerol emulsion.

To determine whether an apolipoprotein-free artificial triacylglycerol emulsion can substitute for VLDL in studying cholesterol ester-triacylglycerol exchange processes between triacylglycerol-rich lipoproteins and cholesterol ester-rich lipoproteins, we used Intralipid to modify human plasma LDL. Intralipid was incubated with LDL in the presence of lipoprotein-poor plasma (d greater than 1.21 g/ml) at 37 degrees C. Intralipid served as an acceptor for cholesterol ester and as a donor of triacylglycerol, modifying the low-density lipoproteins so that triacylglycerol became the major core lipid in the particle - the contribution of cholesterol ester to LDL mass decreased from 38% to 18%, while that of triacylglycerol increased from 4.9% to 26%. On lipolysis most added LDL triacylglycerol (59-72%) was hydrolyzed, resulting in a smaller particle than the "native' LDL particle with net loss of cholesterol ester. Incubation of LDL with the original Intralipid emulsion resulted in modified LDL with a high relative weight of phospholipid (27.7%). On removal of excess phospholipid from Intralipid and incubation of the resultant "washed' Intralipid with LDL, the relative weight of phospholipid in modified LDL decreased to 20%, which was similar to that observed after incubation of LDL with VLDL. We demonstrate that artificial triacylglycerol emulsion can indeed substitute for VLDL in neutral lipid exchange processes, and further confirm that transfer of core cholesterol ester and triacylglycerol occurs independently of the apolipoproteins present in triacylglycerol-rich lipoproteins and LDL.

Cholesterol↗
PubMed1985

Identification of urinary 3-ethoxy-4-hydroxybenzoic and 3-ethoxy-4-hydroxymandelic acids after dietary intake of ethyl vanillin.

It has been discovered recently that several patients undergoing urinary organic acid profiling excrete high concentrations of 3-ethoxy-4-hydroxybenzoic acid and traces of 3-ethoxy-4-hydroxymandelic acid. These are believed to be the consequences of feeding the patients with synthetic diets flavoured with 3-ethoxy-4-hydroxybenzaldehyde, a vanilla-like artificial flavouring added to improve patient acceptance and taste. The syntheses, mass spectra and gas chromatographic behaviour of these and related compounds are presented.

Adult↗
PubMed1985

Multiple hornet stings with features of Reye's syndrome.

Hornet's venom is known to possess a variety of toxic effects. A 19-mo-old girl who developed a Reye-like syndrome following multiple stings by the Oriental hornet (Vespa orientalis) is described. She presented with encephalopathy associated with hepatomegaly, elevated transaminase levels, low prothrombin time, and hyperammonemia. Liver biopsy demonstrated microvesicular fatty infiltration and diffuse mitochondrial changes. Additional features were acute renal tubular necrosis and massive hemolysis.

Antibodies↗
PubMed1985

Platelet function in a case with abetalipoproteinemia.

Platelet aggregation, [14C]serotonin release and platelet malondialdehyde production were determined in a patient with abetalipoproteinemia (ABL) and found to be normal. The patient demonstrated complete absence of apolipoprotein (apo) B and decreased apo A-I concentration in plasma. The high density lipoprotein (HDL) composition of plasma was abnormal, with an increased cholesterol/protein ratio, increased apo E levels and reduced apo C concentration. The patient's platelets, like platelets derived from a normolipidemic control, possessed receptors capable of binding lipoproteins. On incubating washed platelets derived from a control subject with HDL obtained from the ABL patient, an enhancement in platelet function was observed. A similar concentration of HDL derived from the control had the opposite effect, a depression of platelet function. Lipoprotein-deficient plasma (LPDP) derived from the patient, on the other hand, decreased platelet aggregation and [14C]serotonin release in comparison to the LPDP obtained from the control. The normal platelet function observed in the patient appears to be the result of the platelet-enhancing effect of an abnormal HDL, thus compensating for the absence of low and very low density lipoproteins from the patient's plasma which, when present, stimulate platelet function.

Abetalipoproteinemia↗
PubMed1985

Incorporation of [14C]glucose into alpha-1,4 bonds of glycogen by leukocytes and fibroblasts of patients with type III glycogen storage disease.

In two patients assay of alpha-1,6-amyloglucosidase activity by incorporation of [14C]glucose into glycogen revealed normal activity in leukocytes, erythrocytes, and fibroblasts, whereas no activity was detected in liver and muscle. No activity in any tissue was found when enzyme activity was assayed by following the release of glucose from a phosphorylase limit dextrin. Labeling of glycogen by incubation with crude tissue homogenates according to the protocol used for the [14C]glucose method and subsequent degradation of the outer portion of the polysaccharide molecule with beta-amylase showed that with tissues from normal controls more than 90% of the label of the glycogen was retained in the limit dextrin. When fibroblasts or leukocytes of the patients served as enzyme source up to 80% of the label was released after incubation with beta-amylase or phosphorylase a. Addition of Tris to the assay inhibited enzyme activity in fibroblast homogenates of the patients and of controls to the same extent and had no effect on the distribution of the label between supernatant and limit dextrin after beta-amylolysis of the labeled glycogen. A pH curve performed with fibroblast preparations from the patients and a normal control did not reveal differences in the effect of changes in pH on [14C]glucose incorporation. We propose that incorporation of [14C]glucose into glycogen by the enzyme present in the patients' cells was into alpha-1,4 linkages in glycogen.

Cells, Cultured↗
PubMed1985

Is hypertriglyceridemic very low density lipoprotein a precursor of normal low density lipoprotein?

The precursor-product relationship of very low density (VLDL) and low density lipoproteins (LDL) was studied. VLDL obtained from normal (NTG) and hypertriglyceridemic (HTG) subjects was fractionated by zonal ultracentrifugation and subjected to in vitro lipolysis. The individual subfractions and their isolated lipolysis products, as well as IDL and LDL, were rigorously characterized. A striking difference in the contribution of cholesteryl ester to VLDL is noted. In NTG subfractions, the cholesteryl ester to protein ratio increases with decreasing density (VLDL-I----VLDL-III). This is the expected result of triglyceride loss through lipolysis and cholesteryl ester gain through core-lipid transfer protein action. In HTG subfractions there is an abnormal enrichment of cholesteryl esters that is most marked in VLDL-I and nearly absent in VLDL-III. Thus, the trend of the cholesteryl ester to protein ratios is reversed, being highest in HTG-VLDL-I and lowest in VLDL-III. This is incompatible with the precursor-product relationship described by the VLDL----IDL----LDL cascade. In vitro lipolysis studies support the conclusion that not all HTG-VLDL can be metabolized to LDL. While all NTG subfractions yield products that are LDL-like in size, density, and composition, only HTG-VLDL-III, whose composition is most similar to normal, does so. HTG VLDL-I and VLDL-II products are large and light populations that are highly enriched in cholesteryl ester. We suggest that this abnormal enrichment of HTG-VLDL with cholesteryl ester results from the prolonged action of core-lipid transfer protein on the slowly metabolized VLDL mass. This excess cholesteryl ester load, unaffected by the process of VLDL catabolism, remains entrapped within the abnormal particle. Therefore, lipolysis yields an abnormal, cholesteryl ester-rich product that can never become LDL.

Adult↗
PubMed1985

Plasma phospholipid transfer protein enhances transfer and exchange of phospholipids between very low density lipoproteins and high density lipoproteins during lipolysis.

In order to determine the effects of a plasma phospholipid transfer protein on the transfer of phospholipids from very low density lipoproteins (VLDL) to high density lipoproteins (HDL) during lipolysis, biosynthetically labeled rat 32P-labeled VLDL was incubated with human HDL3 and bovine milk lipoprotein lipase (LPL) in the presence of the plasma d greater than 1.21 g/ml fraction or a partially purified human plasma phospholipid transfer protein (PTP). The addition of either the PTP or the d greater than 1.21 g/ml fraction resulted in a 2- to 3-fold stimulation of the transfer of phospholipid radioactivity from VLDL into HDL during lipolysis. In the absence of LPL, the PTP caused a less marked stimulation of transfer of phospholipid radioactivity. Both the d greater than 1.21 g/ml fraction and the PTP enhanced the transfer of VLDL phospholipid mass into HDL, but the percentage transfer of phospholipid radioactivity was greater than that of phospholipid mass, suggesting stimulation of both transfer and exchange processes. Stimulation of phospholipid exchange was confirmed in experiments where PTP was found to augment transfer of [14C]phosphatidylcholine radioactivity from HDL to VLDL during lipolysis. In experiments performed with human VLDL and human HDL3, both the d greater than 1.21 g/ml fraction and the PTP were found to stimulate phospholipid mass transfer from VLDL into HDL during lipolysis. Analysis of HDL by non-denaturing polyacrylamide gradient gel electrophoresis showed that enhanced lipid transfer was associated with only a slight increase in particle size, suggesting incorporation of lipid by formation of new HDL particles. In conclusion, the plasma d greater than 1.21 g/ml fraction and a plasma PTP enhance the net transfer of VLDL phospholipids into HDL and also exchange of the phospholipids of VLDL and HDL. Both the transfer and exchange activities of PTP are stimulated by lipolysis.

Animals↗
PubMed1984

Congenital hepatic fibrosis--unusual presentations.

Two children with congenital hepatic fibrosis presented atypically: one with prolonged fever and hepatomegaly associated with a giant intrahepatic biliary cyst and a second with ascites at an early age despite normal serum albumin concentrations.

Ascites↗
PubMed1984

Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.

The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation of bezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3. HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted of free and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL. Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships. The observations support the concept that most abnormalities reflect the degree of triglyceridemia. We suggest that plasma core-lipid transfer protein(s) is an effector of the abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events.

Adult↗